Abstract

PURPOSE: Clara Cells (CC), non-ciliated epithelial cells prominent in bronchioles, produce a specific protein (CC10) in response to diverse injurious stimuli to the respiratory system. We previously reported an acute increase in CC10 in rat lungs following IV triolein injection in a model of lung damage similar to Fat Embolism Syndrome (FES) in humans. The bronchial and septal CC staining peaked at 24hr post-injection, associated with septal inflammation, fibrosis, bronchitis and vasculitis, persisting at 96hr but with improvement at 264hr. This study purpose is to describe 3 and 6 week CC response to a single triolein dose.

METHODS: With approval by University of Kansas animal-care committee, 22 Sprague-Dawley rats (∼250gm) received 0.2mL of triolein in the caudal vein; 12 control rats received saline (0.2mL IV). Triolein was acutely lethal to 8 rats within 6-8 hr; the remainders were sacrificed at 3 wk (8 triolein-T, 6 controls-C) or 6 wk (6T, 6C). Lungs were harvested, fixed and stained by H&E, trichrome and rat-specific anti-CC10. Pathological changes were coded and graded in lungs according to a previously reported technique.

RESULTS: Large and small bronchi CC staining was more intense in the 3 week triolein-treated rats than the 6 weeks group (P< 0.001), but in both triolein-treated groups the stain intensity was greater than controls (P< 0.001). The same stain was more evident in pneumocytes of triolein treated rats vs. controls, but no difference was observed within the two triolein-treated groups (3wk-6wk). Many macrophages were also strongly CC10 positive with the highest values in triolein-treated rats at 6 weeks (P< 0.001). Increases were also observed in the septal thickness, collagen and inflammation in the same animals.

CONCLUSION: Long-term treatment with triolein was associated with a progressive bronchial decline of CC10 expression. Positively stained macrophages were increased at 6 weeks in association with an increased pulmonary inflammation and fibrosis, suggesting progressive organ damage to lungs but not to the bronchi, after a recovery phase.

Return to: Long-term Effects of Triolein on the Pulmonary Clara Cells in a Rat Model for Fat Embolism Syndrome

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